Poxviruses are a large family of DNA viruses known to infect a variety of mammalian species. To date, approximately 50 poxvirus genomes have been identified and each genome contains about 200 open reading frames encoded therein. The poxvirus family, otherwise known as Poxviridae, includes two subfamilies (Chordopoxvirinae and Entomopoxvirinae) wherein the species are divided into eight and three genuses respectively, including but limited to Orthopoxvirus, Parapoxvirus, Avipoxvirus, Capripoxvirus, Leporipoxvirus, Suipoxvirus, Molluscipoxvirus and Yatapoxvirus, which include but are not limited to the species known as Myxoma Virus, Vaccinia Virus, Swinepox Virus, Molluscum Contagiosum Virus and Yaba Monkey Tumor Virus. Poxviruses are characterized as large, brick-like virions with complex symmetry that share antigenic determinants among different species of the family.
It is well known within the art that, upon infection of a host organism, the poxvirus genome mediates expression of numerous proteins that interfere and modulate homeostasis within the host. In addition to proteins that mediate an intracellular effect, poxviruses are also known to secrete proteins into the circulatory system of the infected animal. Such secreted proteins include agents that bind and inhibit various different aspects of the mammalian immune system and minimize immune-mediated clearance of the virus.
The Yaba Monkey Tumor Virus (YMTV) is poxvirus of the Yatavirus genus and was characterized in 1958 during outbreaks of rhesus monkeys. YMTV infection in monkeys leads to epidermal histiocytomas that advance to suppurative inflammatory reactions. YMTV has a DNA genome of 136 kilobases with a large part of the genome yet to be cloned and characterized. YMTV grows relatively slowly in primate cell culture lines and its host range is restricted to a small number of primates, and occasionally man following accidental exposure to infected monkeys.
IL-18 is a pro-inflammatory mammalian cytokine that plays an important early function in the potentiation of Th1-like immune responses. In addition to its independent effects, IL-18 synergizes with IL-12 to induce IFN-γ production from various immune cell types. Binding of IL-18 to specific cell-surface receptors induces NF-κB activation and IL-18 is important in vivo for production of IFN-γ and inflammatory responses that may contribute to inflammatory disease. These diseases include but are not limited to allergic inflammation, atherosclerotic plaque growth and unstable plaque rupture, arterial restenosis, by-pass graft occlusion, Gaucher's disease, diabetes mellitus, rheumatoid arthritis, multiple sclerosis, transplant rejection, transplant vasculopathy and glomerulonephritis.
This invention provides the non-obvious identification and characterization of a protein derived from YMTV, where said protein is referred to as YMTV Cytokine Inhibitor, or YCI. The invention embodies nucleic acid and amino acid polymers encoding said YCI, including methods of detecting and producing said YCI. The invention further embodies the use of this YCI as a method of modulating the immune response within an organism. It is further claimed herein that the nucleic acid and amino acid sequences disclosed may be utilized for the treatment of human individuals for the purpose of preventing, treating or reversing the onset of one or more immune-related diseases, including inflammation and the immune-mediated diseases outlined above, but not limited to such.